Antimicrobial peptides: Resistant-proof antibiotics of the new millennium

Abstract

(Table Presented) This review encompasses an update on the worldwide research activities made towards developing antimicrobials against the persistent threats from multidrug-resistant gram-negative infection. The lethality of endotoxin or lipopolysaccharide and its conserved bioactive moiety, lipid A, is discussed. We include documentation of our own research efforts towards the development of novel endotoxin antagonists and antimicrobials such as Sushi peptides, derived from the horseshoe crab Factor C, which show great promise for future prophylactic/therapeutic applications. The mechanism of microbicidal action of the Sushi peptides is postulated. In addition to Sushi peptides, we also present other approaches we have undertaken, such as screening for anti-endotoxic peptides from a phage-display library; a computational approach towards rational design of anti-endotoxic and antimicrobial peptides; and finally, a novel alternative that is best analogized by the ancient Chinese medical practice of using "poison to kill poison," which, in modern parlance, entails the innovative application of nonendotoxic Helicobacter pylori lipopolysaccharide/lipid A as a competitor to antagonize the endotoxicity of LPS, and hence, the display of antimicrobial properties. © 2004 Wiley-Liss, Inc.